Acute myeloid leukemia (AML) is one of the most common forms of leukemia in adults and despite advances in treatment the 5 year survival is less than 20-50% in adults and significantly lower in the elderly. The remarkable success in treating one relatively uncommon subset of AML, acute promyelocytic leukemia, with all trans-retinoic acid (ATRA) illustrates the great promise for agents with greater efficacy and less toxicity. Utilizing A TRA, the presumed cure of 75-85% of patients is possible. ATRA's remarkable success stems from the fact that AML is a disease characterized by the arrest of differentiation of immature myeloid cells. A TRA overcomes this block in differentiation by forcing leukemic cells to mature. Unfortunately A TRA does not work clinically for 90-95% of AML patients. We have identified a therapeutic target and an optimized lead compound against this target that leads to differentiation induction in AML patients that are not normally responsive to ATRA. In this application, we will test the clinical utility of this novel agent for AML using mouse model systems. Provide key